Study in Treatment of Collagen-Induced Arthritis in DBA/1 Mice Model by Genistein

This work aimed to evaluate the effects of genistein treatment in Collagen Induced Arthritis (CIA) mouse model.

CIA was elicited in DBA/1 Mice by an intradermal injection of 100 μL of an emulsion of bovine type II collagen (CII) in isovolumic incomplete Freund's adjuvant (IFA) at the base of the tail. Twenty-one days later, a second injection of CII in IFA was administered at the base of the tail. After the symptoms of arthritis showed in mouse model, we divided animals into two groups according to their clinical symptom scores. The treatment group was intraperitoneally injected daily with genistein (based on the pre-experiment data and literature reported, 5 mg/kg dose was selected and tested) for 12 days, while the control group was injected with phosphate buffered saline. Inflammatory cytokines titer, radiological, and histological observations were completed at different time's points after treatment. CT analysis was conducted 3 months after the treatment to observe the articular structures. Immunohistochemical analysis was performed to investigate the expression and distribution of VEGF in joint tissues.

Genistein suppressed the expressions of IL-1β, IL-6 and TNF-α in the serum. Radiological results showed that bone degradation was inhibited by the treatment. Moreover, hematoxylin and eosin staining showed that the degree of inflammation was relieved. In the cartilage area, TRAP stain-positive cells were detected, which was notably reduced in the treatment group compared to the control group. Micro-CT 3D images clearly exhibited that the joint adhered and structures destroyed in the control group with less destruction in the treatment group. Furthermore, genistein suppressed VEGF expression, and blocked angiogenesis in the synovial tissue.

Our work provides further data regarding the effects of genistein as a potential treatment drug for RA, as well as the role of genistein in the anti-inflammatory pathway in RA therapy.